The goal of this project is to improve our understanding of carcinogenesis in gynecological cancers and to better define the morphological criteria and biological behavior. Papillomavirus (condyloma)-related changes have been recognized as the most common squamous abnormalities of the uterine cervix. Although the epidemiological and amorphological findings strongly suggest a cause and effect relationship between cervical condyloma and neoplasia, further proof of this association is hampered by the difficulty in distinguishing papillomavirusinduced atypia from neoplasia by the available morphological criteria. This is exemplified by the fact that 50% of changes classified as mild or moderate dysplasias have detectable papillomavirus structural antigen by immunoperoxidase technique. To circumvent these limitations, nuclear DNA quantitation and immunoperoxidase stain for papillomavirus structural antigen were applied simultaneously to 54 cervical condylomas. All condylomas without nuclear atypia had diploid or polyploid DNA distribution and 61% of these had detectable papillomavirus antigen. In condylomas with varying degrees of nuclear atypia, 59% of those with diploid or polyploid DNA pattern had detectable papillomavirus antigen as compared to only 14% of those aneuploid lesions. The aneuploid dysplasias containing papillomavirus antigen represent a transitional stage between condyloma and true neoplasia. In true neoplasia, the viral antigen cannot be detected by the immunoperoxidase technique, because of the arrest of viral assembly once the viral genome is incorporated into the neoplastic cells. Further studies will be undertaken to determine the frequency of neoplastic transformation in cervical condyloma. Data also suggest that 64% of urethral condylomas studied by immunoperoxidase method contained papillomavirus antigen.